Evaluating Risks from Antibacterial Medication Therapy

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Evaluating Risks from Antibacterial Medication Therapy University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Summer 2010 Evaluating Risks from Antibacterial Medication Therapy Sharon B. Meropol University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Therapeutics Commons Recommended Citation Meropol, Sharon B., "Evaluating Risks from Antibacterial Medication Therapy" (2010). Publicly Accessible Penn Dissertations. 424. https://repository.upenn.edu/edissertations/424 A version of Chapter 3 has been published: Meropol SB, Chen Z, Metlay JP. Reduced antibiotic use for acute respiratory infections in adults and children. Br J Gen Prac. Oct. 2009; 59(567)3321-328.DOI:10.3399/ bjgp09X472610. E321-328 PMID: 19843412 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/424 For more information, please contact [email protected]. Evaluating Risks from Antibacterial Medication Therapy Abstract ABSTRACT EVALUATING RISKS FROM ANTIBACTERIAL MEDICATION THERAPY USING AN OBSERVATIONAL PRIMARY CARE DATABASE Sharon B. Meropol Joshua P. Metlay Virtually everyone in the U.S. is exposed to antibacterial drugs at some point in their lives. It is important to understand the benefits and risks elatedr to these medications with nearly universal public exposure. Most information on antibacterial drug-associated adverse events comes from spontaneous reports. Without an unexposed control group, it is impossible to know the real risks for treated vs. untreated patients. We used an electronic medical record database to select a cohort of office visits for non-bacterial acuteespir r atory tract infections (excluding patients with pneumonia, sinusitis, or acute exacerbations of chronic bronchitis), and compared outcomes of antibacterial drug-exposed vs. -unexposed patients. By limiting our assessment to visits with acute nonspecific espirr atory infections, we promoted comparability between exposed and unexposed patients. To further control for confounding by indication and practice, we explored methods to promote further comparability between exposure groups. Our rare outcome presented an additional analytic challenge. Antibacterial drug prescribing for acute nonspecific respiratory infections decreased over the study period, but, in contrast to the U.S., broad spectrum antibacterial prescribing remained low. Conditional fixed effects linear regression provided stable estimates of exposure effects on rare outcomes; results were similar to those using more traditional methods for binary outcomes. Patients with acute nonspecific espirr atory infections treated with antibacterial drugs were not at increased risk of severe adverse events compared to untreated patients. Patients with acute nonspecific espirr atory infections exposed to antibacterials had a small decreased risk of pneumonia hospitalizations vs. unexposed patients. This very small measurable benefit of antibacterial drug therapy for acute nonspecific espirr atory infections at the patient level must be weighed against the public health risk of emerging antibacterial resistance. Our data provide valuable point estimates of risks and benefits that can be used ot inform future decision analysis and guideline recommendations for patients with acute nonspecific espirr atory infections. Ultimately, improved point-of- care diagnostic testing may help direct antibacterial drugs to the subset of patients most likely to derive benefit. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Epidemiology & Biostatistics First Advisor Joshua P. Metlay, MD, PhD Keywords anti-infective agents, databases, health services research, prescriptions, respiratory tract infections, drug toxicity Subject Categories Therapeutics Comments A version of Chapter 3 has been published: Meropol SB, Chen Z, Metlay JP. Reduced antibiotic use for acute respiratory infections in adults and children. Br J Gen Prac. Oct. 2009; 59(567)3321-328.DOI:10.3399/bjgp09X472610. E321-328 PMID: 19843412 This dissertation is available at ScholarlyCommons: https://repository.upenn.edu/edissertations/424 EVALUATING RISKS FROM ANTIBACTERIAL MEDICATION THERAPY USING AN OBSERVATIONAL PRIMARY CARE DATABASE Sharon B. Meropol A DISSERTATION in Epidemiology Presented to the Faculties of the University of Pennsylvania in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2010 Supervisor of Dissertation Signature Joshua P. Metlay, M.D., Ph.D. Associate Professor of Medicine & Epidemiology Graduate Group Chairperson Signature Daniel F. Heitjan, Ph.D., Professor of Biostatistics & Statistics Dissertation Committee Jalpa A. Doshi, Ph.D., Research Assistant Professor of Medicine A. Russell Localio, Ph.D. Associate Professor of Biostatistics Paul R. Rosenbaum, Ph.D. Professor of Statistics Brian L. Strom, M.D., M.P.H., Professor and Chair, Biostatistics & Epidemiology EVALUATING RISKS FROM ANTIBACTERIAL MEDICATION THERAPY USING AN OBSERVATIONAL PRIMARY CARE DATABASE© 2010 Sharon B. Meropol Dedication For Neal, Dan and Hannah iii Acknowledgement I thank the faculties of the University of Pennsylvania Department of Biostatistics and Epidemiology and the Center for Clinical Epidemiology and Biostatistics for their mentorship and consistently open doors and minds. I’m particularly grateful to Brian Strom for providing me the opportunity to be part of this exceptional community, to Josh Metlay for his scholarship, lucidity, patience, and endless optimism, and to the members of my Committee for giving me the gifts of their time, support, intellect, and inspiration. Special thanks go to Neal, Dan, and Hannah for their continual support and love. Zhen Chen provided statistical support for the early part of this work, especially Chapter 3. All authors have no competing interests to disclose This work was supported in part by a Ruth L. Kirschstein National Research Service Award (grant number F32-AI-073015-01A1) from the National Institute for Allergy and Infectious Diseases, an Agency for Healthcare Research and Quality (AHRQ) Centers for Education and Research on Therapeutics cooperative agreement (grant number U18-HS-016946) from the Agency for Healthcare Research and Quality, by an NIH Clinical and Translational Science Award (grant UL1-RR02-4134) and by a grant from CDC EPIC, London, U.K.. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. This work was presented, in part, at the Pediatric Academic Societies Annual Meeting, May 4, 2008, Honolulu, HA, and the 4th Annual International Conference on Pharmacoepidemiology & Therapeutic Risk Management, August 20, 2008, Copenhagen, Denmark. The limited dataset used in this study is covered by a data use agreement between the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania and EPIC Database Research Company. EPIC is a licence holder of an historical part of the GPRD dataset. GPRD is owned by the Secretary of State for Health and is managed on his behalf by the GPRD Group at the MHRA. The name GPRD is a trade mark of the GPRD group. iv This study was granted exempt status by the University of Pennsylvania Institutional Review Board, and approval by both the University of Pennsylvania THIN User Committee and EPIC Database Research Company in the U.K. v ABSTRACT EVALUATING RISKS FROM ANTIBACTERIAL MEDICATION THERAPY USING AN OBSERVATIONAL PRIMARY CARE DATABASE Sharon B. Meropol Joshua P. Metlay Virtually everyone in the U.S. is exposed to antibacterial drugs at some point in their lives. It is important to understand the benefits and risks related to these medications with nearly universal public exposure. Most information on antibacterial drug-associated adverse events comes from spontaneous reports. Without an unexposed control group, it is impossible to know the real risks for treated vs. untreated patients. We used an electronic medical record database to select a cohort of office visits for non-bacterial acute respiratory tract infections (excluding patients with pneumonia, sinusitis, or acute exacerbations of chronic bronchitis), and compared outcomes of antibacterial drug-exposed vs. -unexposed patients. By limiting our assessment to visits with acute nonspecific respiratory infections, we promoted comparability between exposed and unexposed patients. To further control for confounding by indication and practice, we explored methods to promote further comparability between exposure groups. Our rare outcome presented an additional analytic challenge. Antibacterial drug prescribing for acute nonspecific respiratory infections decreased over the study period, but, in contrast to the U.S., broad spectrum antibacterial prescribing remained low. Conditional fixed effects linear regression provided stable estimates of exposure effects on rare outcomes; results were similar to those using more traditional methods for binary outcomes. Patients with acute nonspecific respiratory infections treated with antibacterial drugs were not at increased risk of severe adverse events compared to untreated patients. Patients with acute nonspecific respiratory infections exposed to antibacterials had a small decreased risk of pneumonia hospitalizations vs. unexposed patients. This very small measurable benefit of antibacterial drug therapy for acute nonspecific respiratory infections at the patient level must be weighed against the public
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